System, formulation, kit and method for tagging colonic residue in an individual

ABSTRACT

This invention relates to a colonic residue tagging system, formulation, kit and method for use in preparing an individual for a predetermined activity which requires tagging at least some colonic residue in a digestive tract such that a medically and/or diagnostically useful procedure can be performed on the digestive tract. Such predetermined activity includes, but is not limited to, colon screenings. In one alternative embodiment, a dietary regimen comprising low residue foods is coordinated with the colonic residue tagging regimen, prior to a predetermined activity, thereby resulting in tagged stool such that a medically or diagnostically useful procedure can be performed on the digestive tract. The present invention also provides an individual sufficient amounts of fluids and nutrition while minimizing the amount of stool formation prior to the predetermined activity. In another alternative embodiment, the foods comprise an effective amount of tagging agent, such that when the food is consumed over time, at least some of the colonic residue in the digestive tract will be sufficiently tagged so that a medically or diagnostically useful procedure can be performed on the digestive tract

CROSS REFERENCE TO OTHER APPLICATIONS

This application claims priority from U.S. Provisional Application Ser.No. 60/370,661, filed Apr. 6, 2002, which is incorporated herein byreference in its entirety.

I. FIELD OF THE INVENTION

This invention relates to a system, formulation, kit and method for usein tagging colonic residue, such as stool, in an individual prior to apredetermined activity, including but not limited to a medical ordiagnostic procedure. In one alternative embodiment, the presentinvention provides an individual one or more doses of a tagging agent,together with sufficient fluids and nutrition to enable the individualto conduct daily, routine activities while minimizing the amount ofstool formation prior to the predetermined activity.

II. BACKGROUND OF THE INVENTION

As used herein the term “digestive trace” includes, but is not limitedto, the mouth, pharynx, esophagus, stomach, small intestine and largeintestine. Also, as used herein, the terms “colonic residue” and“residue” include any composition of matter resulting from digested foodand other body waste which has not been absorbed by the body's digestivesystem. Such residue includes, but is not limited to, any solid,semi-solid or liquid stool matter.

Removal of stool matter from the digestive tract has historically beennecessary to effectively screen for gastrointestinal abnormalities,including, but not limited to, cancer such as colon cancer. Since coloncancer is a highly treatable and often curable if detected early,screening tests for detecting premalignant polyps and colorectal cancersat stages early enough for complete removal are very important.

Colon screening procedures include, for example, barium enema,sigmoidoscopy and fiberoptic colonoscopy. The most recent technologicaladvancement in colon screening is virtual colonoscopy/CT Colonography.This procedure utilizes computer reformation of radiologic images toform images of the colon in two or three dimensions. Historically,sufficient amounts of stool matter had to be removed from the colonprior to a virtual colonoscopy procedure. This is because stool andcolon lesions are not easily distinguishable in computer tomography orother radiologic modality images, thus preventing physician's ability todistinguish pathology from retained fecal debris. In one alternativeembodiment, the present invention is a method for marking colonicresidue (e.g., stool) present in an individual's digestive tract (e.g.,colon) with a radiopaque material before the digestive tract is imaged.The marked stool, for example, can then be readily identified in theimages. Alternatively, the marked stool can be identified and/orelectronically removed from the images.

U.S. Pat. No. 6,477,401 to Johnson et. al. is directed to a method ofgenerating colonography images of a patient's unprepared colon forcolorectal screening. This method requires providing the patient atleast 10 grams of stool marker in doses over at least a 48 houradministration period.

The present invention is distinguishable, and is more advantageous overthe methods disclosed in the '401 patent. For example, in onealternative embodiment of the present invention, the individual's stoolis sufficiently marked within 24 hours. This improves the patient'scompliance to the tagging and/or dietary regimen prior to thepredetermined activity. Also, in contrast to the '401 patent, in onealternative embodiment, the present invention limits the amount oftagging doses to 3 or less over a 24-hour administration period. This isaccomplished by providing small volumes of liquid containing highconcentrations of tagging agent. Further, the present inventionminimizes the amount of stool retained in the gastrointestinal tract(e.g., colon) by administering a low residue diet to the individualprior to the predetermined activity. This provides several advantages.For example, in some situations, the physician may require theindividual to undergo a laxative prior to the predetermined procedure.Because the present invention minimizes the production of stool, thepatient need only take a mild laxative, as opposed to a cathartic. Also,because low amounts of stool are present, there is no need to utilizespecial software to remove the marked stool from the images of theindividual's tissue, for example. All considered, the present invention,in contrast to the '401 patent, provides a cleaner gastrointestinaltract (e.g., colon) with less fluid and less retained stool. Otheradvantages of the present invention are described herein.

There is, therefore, a need for a colonic residue tagging regimen whicheffectively marks colonic residue in the digestive tract while providingthe user with a sufficient level of calories and nutrition to conductroutine, daily activities. Additionally, there is a need for a taggingregimen which is readily useable and convenient, which also minimizesthe amount of fluid or stool formation prior to the predeterminedactivity. In addition, there is a need for a dietary regimen to be usedin conjunction with a tagging regimen, while at the same timefacilitating user compliance since current tagging regimens aredifficult or painful to complete. The consequences of non-compliance canbe great. For example, noncompliance can result in an ineffective colonscreening.

III. SUMMARY OF THE INVENTION

It is an object of the present invention to provide an easy andeffective colonic residue tagging system, formulation, kit and methodfor use in preparing an individual prior to a predetermined activitywhich requires tagging at least some colonic residue.

It is also an object of the present invention to provide a low residuedietary system, formulation, kit and method to be used with a taggingregimen for preparing individuals for a predetermined medical diagnosticprocedure including, but not limited to, colon screening.

Further, it is an object of the present invention to provide a varietyof individually prepackaged, ready to eat or easy to prepare solid orliquid foods which can be consumed as part of a regimen for tagging atleast some colonic residue in the digestive tract prior to apredetermined activity.

It is also an object of the present invention to provide a variety offoods containing an effective amount of tagging agent, such that whenthe food is consumed, at least some of the colonic residue in adigestive tract will be sufficiently tagged so that a medically and/ordiagnostically useful procedure can be performed on the digestive tract.

It is another object of the present invention to provide a low residuedietary regimen comprising sufficient calories and nutrition such thatroutine, daily activities may be performed and no nutritional detrimentis suffered by the user while undergoing the dietary regimen inconjunction with a colonic residue tagging regimen in preparation of apredetermined activity.

Other objects, features, and advantages of the present invention will beapparent to those of ordinary skill in the art in view of the followingdetailed description of the invention and drawings.

IV. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a non-limiting example of a container comprising the fooditems of the present invention.

FIG. 2 is a non-limiting example of a kit comprising the food items ofthe present invention, along with one or more doses of a tagging agent.

FIG. 3 is a non-limiting diagram of a dietary regimen and taggingregimen of the present invention.

FIG. 4 is a non-limiting diagram of an alternative embodiment of thepresent invention.

FIG. 5 is a non-limiting diagram of an alternative embodiment of thepresent invention.

FIGS. 6-12 are radiographic images of a cross section of an abdomen,including portions of a colon, illustrating an example of the type ofstool marking that would be present when an individual's digestive tractis prepared in accordance with the present invention.

V. DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a colonic residue tagging system, kit,formulation and method for use in preparing an individual for apredetermined activity, including but not limited to, an activity whichrequires tagging at least some colonic residue in a digestive tract. Asused herein, the phrase “tagged digestive tract” or phrases similarthereto, include but are not limited to a digestive tract that has atleast some colonic residue marked with a tagging agent such that atleast some of the residue can be differentiated from surroundingtissues.

A predetermined activity includes, but is not limited to, any activityimaging a tagged digestive tract. In one embodiment, the predeterminedactivity may include, but is not limited to, a medical diagnosticprocedure, which includes, but is not limited to, gastrointestinalscreening (e.g., colon screening) such as virtual endoscopy, whichincludes, but is not limited to, CT colonography and MR colonography.Other diagnostic procedures may include ultrasound, flat panel imagingmethodologies, sigmoidoscopy, endoscopy or fiberoptic colonoscopy. Othermethodologies may be performed in a conventional manner such as, forexample, those described in U.S. Pat. No. 5,891,030; U.S. Pat. No.5,782,762 and U.S. Pat. No. 5,920,319. The images generated from theabove procedures may be three dimensional (3D) images. Commerciallyavailable software programs such as Voxel/View from Vital Images may beused for this purpose. Alternatively, the screening diagnoses can beobtained through the use of two dimensional (2D) colonography imagesprocessed in accordance with the methodologies identified herein. In onealternative embodiment, the present invention is a method of markingcolonic residue with identifiable material before one or more sectionsof the digestive tract is imaged.

The present invention also provides for a combined low residue dietaryand colonic residue tagging system, kit, formulation and method for usein preparing an individual for a predetermined activity. The dietaryregimen of the present invention comprises one or more food items. Theseitems include any liquid, solid or semi-solid food providing, in wholeor in part, the requisite amounts of nutrition described herein. Suchfood items may include, but are not limited to, soup products, proteinsupplements, grain foods, starch foods, fruit or vegetable foods,nutritional drinks or beverages.

International Appl. No. PCT/US01/32039 and U.S. application Ser. No.10/177,276 relate to a nutritional dietary system, formulation, kit andmethod for use in preparing an individual for a predetermined activity.Both of these applications are incorporated herein by reference. Suchapplication discloses several nutritional dietary regimens. Each ofthese dietary regimens are suitable for use in the present invention,provided the requisite amount of tagging agent is incorporated into thedietary regimen, as discussed herein.

In use, the colonic tagging agents of the present invention arepreferably consumed over about a 20-to 36-hour period, or a 20- to48-hour period, or a 20- to 36-hour period, or a 24- to 28-hour period,more preferably over about a 24-hour period prior to a predeterminedactivity. In addition, the food items of the present invention, togetherwith suitable tagging agents, may be consumed over a 72-hour period, a48-hour period, a 24- to 36-hour period, a 36- to 48-hour period and 48-to 72-hour period prior to a predetermined activity.

A. Tagging Regimens

The tagging agents of the present invention may include any compositionthat can label and/or mark colonic residue so that such residue can bedifferentiated from surrounding tissue during a predetermined activity.Suitable tagging agents, include but are not limited to, barium-basedcompounds, such as barium sulfate, for example. Other agents may includeiodine-based compounds, such as non-ionic or ionic iodine or anycombination of the above mentioned compounds.

In the present invention, doses of tagging agent may be administered ina liquid, semi-liquid, powder or solid form. For example, the taggingagent may be consumed as a drink. Also, the tagging agent may beconsumed as a suspension or swallowed as a tablet, capsule or caplet. Inanother alternative embodiment, the total amount of tagging agentadministered to the individual prior to the predetermined activity maybe at least 1 g, 5 g, 10 g, 50 g, 70 g, 10 g, 150 g, 200 g, 300 g, 350g, 400 g, 450 g, 500 g, 550 g, 600 g or more. The preferred amountranges from about 15 g to 30 g, more preferably about 20 g to about 30g.

In addition, the tagging agent can be incorporated into any of the fooditems in the present nutritional dietary system described herein. Forexample, the tagging agent may be added to a pudding, yogurt-like foodproduct, soup nutritional drink or other food item with or withoutnutritional value. Methods for including the tagging agent into the fooditem(s) may include adding the agent while the food is being prepared orcooked, or it may be added afterwards. For example, the tagging agentmay be added directly to pre-made yogurt-like food products, pudding,nutritional drinks or soups, for example. The amount of tagging agent inthe one or more food items may range from about 0.01 g to about 200grams; 0.01 g to about 150 g; 0.01 g to about 100 g; 0.01 g to about 50g; 0.01 g to about 25 g; 0.01 g to about 5 g; 0.01 g to about 1 g; 0.01g to about 700 mg. In all, the total amount of tagging agent consumed bythe individual prior to the predetermined activity may be at least 1 g,5 g, 10 g, 50 g, 70 g, 100 g, 150 g, 200 g, 250 g, 300 g, 350 g, 400 g,450 g, 500 g, 550 g, 600 g or more. In another alternative embodiment,the food item (containing tagging agent) may be consumed over a 20- to48-hour period, or a 36- to 48-hour period; or a 48- to 72-hour periodor a 24- to 28-hour period. Such food item may also be administered overa 3- to 5-day period.

In the present invention, the tagging agent may be provided in asuspension. Such suspension may comprise water, a sugar-based compound,viscosity agents, such as citric acid and suspending agents or gums. Inone alternative embodiment, the commercially available product Tagitol®may be used in the present invention. Tagitol® is sold by E-Z-EM,Westbury, N.Y. Tagitol® is a low-density suspension of barium sulfate.It is lemon-lime-flavored and provided in 250 ml dose bottles.

In the present invention, an individual may receive 1 to 10 doses oftagging agent over a period of 1-5 days. Each individual dose may rangefrom 0.1 to 100% w/v tagging agent. In one alternative embodiment, thedosing regimen for the tagging agent is administered over a20-to-36-hour period, preferably a 24-hour period, may be as follows:Dose % W/V Tagging Agent 1  50 ml  40% 2 250 ml 2.1% 3 250 ml 2.1% 4 250ml 2.1% 1 250 ml 2.1% 2 250 ml 2.1% 3 250 ml 2.1% 1  20 ml  40% 2  20 ml 40% 3  20 ml  40%

In another alternative embodiment, an individual may receive 1, 2, 3, 4,5, 6, 7, 8, or 9 doses of tagging agent over a period of about 48 hours,or 36 hours, preferably 20- to 24-hours, most preferably 24 hours.Preferably, the individual receives less than 7, 6, 5,4, 3 or 2 dosesover a 48-hour, or 36-hour, preferably 20 to 24 hours, most preferably a24-hour period. In another alternative embodiment, the individual mayreceive only 1 or 2 doses over a 16, 15, 14, 13,12, 11, 10, 9, 8, 7, 6,5, 4, 3, 2 or 1 hour period prior to the predetermined activity.

The volume of each individual dose may range from about 10 ml to about500 ml; about 10 ml to about 400 ml; about 10 ml to about 300 ml; about10 ml to about 250 ml; about 10 ml to about 200 ml; about 10 ml to about100 ml; about 10 ml to about 50 ml. In one alternative embodiment, thevolume of each individual dose may range from about 20 ml to about 60ml; about 20 ml to about 50 ml; about 20 ml to about 40 ml; or about 20ml to about 30 ml.

Each individual dose may range from about 2% to 100%; about 2% to 90%;about 2% to 80%; about 2% to 70%; about 2% to 60%; about 2% to 50%;about 2% to 45%; about 2% to 40%; about 2% to 35%; about 2% to 30%; orabout 2% to 25% w/v tagging agent. The dose may also range from about10% to 80%; 15% to 75%; 20% to 70%; 25% to 55%; 30% to 60%; 35% to 55%;or 40% to 50% w/v tagging agent. Further, the dose may range from about1.5% to 60%, 1.5% to 50%; 1.5% to 40%; 1.5% to 30%; 1.5% to 20%; 1.5% to10%.

In another alternative embodiment, an individual may receive less than 7doses. Each individual dose comprising greater than 2% w/v taggingagent. Also, the doses may be administered over about a 24-hour period.

Each of the above-described doses may take the form of a liquidsuspension and/or be administered by suspending the tagging agent in aliquid whereby the individual drinks the liquid. The process of thepresent invention may be practiced without administering the taggingagent in pill form. Also, the tagging agent may be incorporated into afood item, as described herein.

In one alternative embodiment, the final dose of tagging agent isadministered to the individual at least 12 hours prior to thepredetermined activity. In another alternative embodiment, the finaldose of tagging agent may be administered about 16, 15, 14, 13, 12, 11,10, 9, 8, or 7 hours prior to the predetermined. This dosing regimenenables the individual to sleep through the night without waking up toconsume one or more doses of tagging agent the night before thepredetermined activity. For example, the final dose of the tagging agentmay be administered with the individual's dinner the night before thepredetermined activity.

In one alternative embodiment, the tagging agents may be combined with asugar-based compound. Such compounds may include any simple sugarcompounds, or any, other transient compound or agent capable of causingthe small bowel to hyperscret fluid. This in effect partially fills thesmall bowel with fluid increasing the total volume of contents in thesmall bowel, thus causing an increase in the peristaltic activityresulting in rapid transport of the tagging agent into the colon. Whenthe tagging agent arrives in the colon it is sufficiently mixed with thecolonic residue and body fluids. The transport of this volume causes thecolon to evacuate it's contents to make room for the contents comingdown through the system. The low residue and fiber structure of thenutritional system leaves at least some of the residue tagged.

The sugar-based compounds for use in the present invention may include,but are not limited to, manosacchorides and polysaccharides such asD-mannose, D-galactose, nanionic seed polysaccharide, straight chainmann grouping with branching on every mannose by one gluctose unit,Beta-D-man, alpha-D-gal, D-glcA, D-galA, L-gul, beta-D-man, alpha-D-gal(4:1), D-glucuronic aced, D-galacturones aud, L-glucuronic acid,sorbitol, manotol. The preferred sugar-based compounds are Sorbitol orMannitol.

The preferred amount of Sorbitol and or Mannitol to be combined with thetagging agent is about 0.1% to about 3% or about 1.5 to about 2.5% byvolume, or up to any amount below the USP manograph standard forlaxative concentration levels for these compounds. For example, apreferred tagging regimen may include administering a suspensioncomprising 40% Barium Sulfate and 1.5% or 2.5% Sorbitol to anindividual.

The low residue and low fiber design of the nutritional diet yieldsminimal residue in the colon, thus reducing the requirement tothoroughly clean the colon before a medical diagnostic procedure, forexample. Remaining residue in the colon is tagged for easydifferentiation from surrounding tissue.

In one alternative embodiment, by undergoing the dietary regimen of thepresent invention, a predetermined volume of fluid is delivered to theGI tract. Additionally, the individual takes the tagging agent and allof these components contribute to the controlled fluid intake of theindividual. While the nutritional components satiate the individual theyintroduce sufficient volume of fluid in combination with the taggingagent and the increased peristaltic effect of the sorbital or sorbitallike components in the tagging agent. By controlling the volume offluid, the body evacuates the contents of the colon to make room for thecontents that are transiting through the small bowel.

U.S. Pat. No. 5,782,762 describes preparing a patient's colon by feedingthe patient a low residue diet combined with a contrast agent (such aslow density barium, for example, 1.5% w/v barium) for about 3 days.According to the patent, this procedure serves to homogeneously opacityany retained stool so that the image of the feces can be subtracted fromthe final display using image processing techniques. By contrast, in onealternative embodiment of the present invention, the tagging agentimpregnates the stool non-homogeneously. That is, the tagging agent isdistributed non-uniformly based on the stool's structure. Stool densityvaries within a certain volume of stool. It can range from dense to thinbased on the material or waste in the stool.

B. Hydration

In using the present invention, it is necessary that the individualmaintain sufficient hydration. Such hydration being sufficient tomaintain the individuals normal physiological properties, and to controlthe amount of fluid retained in the digestive tract.

Thus, the dietary and tagging regimen of the present invention may beused with a hydration regimen. Suitable hydration regimens include, butare not limited to, regimens requiring at least some fluid intake,including, but not limited to, water or fruit drinks. The hydrationportion of the present invention is structured to replace the water lostthrough normal voiding (urination) respiration and persperation. Bylimiting the intake of fluids, the patient's normal physiologicalproperties are maintained, and the amount of fluid present in thepatient's bowel is reduced. This goal may be complemented by not havingto use an aggressive cathartic like PEG or any of the saline cathartics.

Excessive fluid intake can generate fluid levels in the colon that canhide and/or obscure normal and pathologic segments of the colon during amedical diagnostic procedure, such as virtual colonoscopy. Thus, asuitable amount of fluid intake for use in the present invention is onethat replaces the fluids used by the body while not creating fluidlevels in the colon that can hide and/or obscure normal pathologicsegments in the colon which otherwise adversely affect the outcome ofpredetermined activity.

In one embodiment, based on about a 20- to 24-hour regimen, the fooditems and doses of tagging agent may collectively provide at least about1 to 4 liters of fluid, preferably about 1 to 3.5 liters, morepreferably about 1 to 3 liters or 1.5 to 2 liters. If the food items anddoses of tagging agent do not provide these amounts of fluid, thepresent invention may be supplemented or the individual may be providedwith additional fluids to achieve such amounts during that period oftime. It has been discovered that controlling or regulating theindividual's fluid intake to the above specified amounts greatlyimproves the readiness of the individual's gastrointestinal tract (e.g.,colon) for the predetermined activity (e.g., colon screening). Forexample, the greater fluid presence in an area of stool, the lower theconcentration of tagging agent, rendering a lower Hounsfield value (HU)for that particular area. The denser the stool, the less fluid present,causing increased concentration of the tagging agent in the stool. Thehigher the tagging agent concentration, the higher the HU for thatparticular area of stool. Increasing the HU value allows for easydifferentiation between stool and surrounding tissues, recognizing thatuntagged stool has a similar density to that of the surrounding normalor pathological tissues.

C. Nutrition

1. Calories

The food items of the present invention may collectively provide anindividual an appropriate caloric intake level over the time period inwhich the invention is utilized. In one alternative embodiment, based onabout a 20 - to about a 36 -hour dietary regimen, the food items maycollectively provide at least 100 calories, preferably in a range ofabout 400 to about 3,000 calories, and more preferably in a range ofabout 600 to about 2,000 calories. In an alternative embodiment, basedon about a 20- to 36-hour dietary regimen, the food items maycollectively provide more than about 600 calories, more preferably in arange of about 1,000 to about 1,800 calories, and most preferably in arange of about 1,500 to about 1,600 calories. In another alternativeembodiment, the food items may collectively provide a range of about1,000 to about 2,000 calories, from about 1,400 to about 1,600 calories,and from about 1,600 calories. The total calories of the food items ofthe present invention are preferably sufficient to enable an averagesized individual to perform routine daily activities withoutexperiencing the dizziness, fatigue and lightheadedness ordinarilyexperienced with a clear liquid diet.

2. Dietary Fiber

The food items of the present invention may collectively provide anindividual an appropriate amount of dietary fiber over the time periodin which the invention is utilized. In one alternative embodiment, basedon about a 20- to 36-hour dietary regimen, the food items maycollectively provide at least 0.5 g of dietary fiber, preferably in arange of about 0.5 g to about 50 g of dietary fiber, more preferably ina range of about 0.5 g to about 20 g, and even more preferably in arange of about 2 g to about 15 g, and most preferably from about 2 g toabout 6 grams. In an alternative embodiment, based on about a 20- toabout a 36-hour dietary regimen, the food items may collectively provideless than about 15 g of dietary fiber. Also, in an alternativeembodiment, based on about a 20- to about a 36-hour dietary regimen, thefood items may collectively provide about 20 g to about 60 g of dietaryfiber, or 20 g to 30 g, 30 g to 40 g, 40 g to 50 g, 50 g to 60 g, or 60g to 100 g. It has been found that a dietary regimen containing lowamounts of dietary fiber, when used in conjunction with a taggingregimen, can eliminate the need for consuming high-volume purgativedrinks or high sodium cathartic cleansing drinks, which can be difficultto consume for some individuals. Examples of foods that may be consumedby a patient on a low residue, low fiber diet are listed in Table I inU.S. Appl. No. 60/370,661. Also, in this application, Table 2 lists anexample of a 24-hour low fiber diet that may be used in the presentinvention.

The food items of the present invention may also collectively provide anappropriate amount of protein, carbohydrates, fats, sodium, potassium,sugars, vitamins or minerals over the time period in which the inventionis utilized by an individual.

Suitable amounts of these nutrients are set forth at pages 9-16 of U.S.Prov. Appl. No. 60/370,661.

3. Solid-Material

The individual food items of the present invention may individually orcollectively provide a suitable amount of solid material, which includesparticulate material. In one alternative embodiment, based on about a20-to about a 36-hour dietary regimen, the present invention may provideup to approximately 1000 grams of solid material, as measured in dryform. In another embodiment, the present invention provides about 10 gto about 1000 grams of solid material, preferably about 100 g to about800 g, more preferably about 200 g to about 700 g, and most preferablyabout 400 g to about 600 g. Table 5 shows the approximate total weightof one alternative embodiment of the dietary regimen of the presentinvention: TABLE 5 Example of Approximate Dry Weight of Dietary RegimenApproximate Approximate Net Food Item Weight Dry Weight PreparedStroganoff  37.62  163.11 Chicken Noodle Soup  36.39  160.88 PotatoPoppers  29.36  29.36 Applesauce  70.15  113.40 Vanilla Shake (3)  66.96(3)  261.46 (3) Lemon Drink Mix (2)  6.95 (2)  216.13 (2) ChocolatePower Bar (2)  50.69 (2)  50.69 (2) Total 489.68 1784.77 TotalPercentage of Solid  27.4 — Material Included in Diet

In another alternative embodiment of the present invention, based onabout a 20-to about a 36-hour dietary regimen, the food items maycollectively comprise at least about 1% by weight of solid material,preferably in a range of about 1% to about 70%, more preferably about10% to about 30%, and most preferably about 20% to about 30%. In anotherembodiment, the food items of the present invention may collectivelyprovide about 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to80%, 80% to 90%, and 90% to 100% by weight of solid material. In anotherembodiment, the food items of the present invention, individually orcollectively, provide sufficient solid material to cause naturalperistalsis in the digestive tract when consumed.

D. Food Items of the Present Invention

The present invention comprises one or more food items, including, butnot limited to soup products, protein supplements, grain foods, starchfoods, fruits or vegetables, nutritional drinks, and beverages. Specificfood items suitable for the present invention are described inInternational Appl. No. PCT/US01/32039 and U.S. application Ser. No.10/177,276, which are incorporated herein by reference. Each food itemof the present invention may be individually prepackaged. In addition,one or more of the food items may be nutritionally enhanced byfortification of vitamins and minerals.

A food item suitable for use in the present invention is one that formsno residue in the digestive tract or that forms an amount of foodresidue which does not impede or otherwise adversely affect apredetermined activity. Individual food items of the present inventionmay be in the form of solids, semi-solids or liquids and may include,but are not limited to, soup products, protein supplements, grain foods,starch foods, fruit or vegetables foods, nutritional drinks andbeverages. In contrast to the prior art, the liquid food items of thepresent invention may or may not be clear. Each of the food items of thepresent invention are discussed in more detail below.

The coloring used in the food items of the present invention,particularly in the nutritional drinks and beverages, may be limited bythe purpose for which the food residue is being removed from theindividual's digestive tract. For instance, a food item containing redcoloring may not be suitable for an individual preparing for an opticalcolonoscopy, as the red coloring may interfere with the test results ofsuch procedure.

As discussed, the tagging agent may be added to a food item. One or moresuch foods may be included in the meal kit described herein.

E. Synergistic Effect When Utilizing Nutrition/Hydration/Tagging

If no laxative is used to cleanse the colon prior to the predeterminedactivity, it was believed that the retained stool would impede thescreening procedure. Surprisingly, however, it has been discovered thatno laxative regimen is required, because the dietary regimen providesmanageable amounts of retained stool, and the amount of stool is suchthat it can be sufficiently tagged with a tagging agent. By combining anappropriate nutrition, hydration and/or tagging regimen, CT or MRColonography may be performed without a colon cleansing system, thusfurther increasing patient compliance. If the predetermined activityrequires bowel cleansing, then the individual need only be given a mildlaxative, as opposed to a cathartic. Additionally, by combining anappropriate nutrition, hydration and/or tagging regimen, the images ofthe individual's gastrointestinal tract (e.g., colon) maybe screened forabnormalities (e.g., cancer) without removing (electronically orotherwise) the marked stool from the images. That is, the images may bescreened for the presence of any abnormalities with the marked stoolpresent in the images.

F. Patient Compliance

Other features of the present invention include improved user complianceand quality of life as compared to conventional techniques for preparingan individual for a medical diagnostic procedure, such as a colonoscopy.For example, the present invention requires less doses of tagging agentto be administered, and the volume of each dose is less than thoseadministered in the prior art. Also, the tagging regimen of the presentinvention may be completed in less than 48 hours, for example. In someinstances, the tagging regimen may be completed in 24 hours, or less.Further, the present invention minimizes the amount of stool retained inthe gastrointestinal tract (e.g., colon). This provides severaladvantages. For example, in some situations, the physician may requirethe individual to undergo bowel cleansing prior to the predeterminedprocedure. Because the present invention minimizes the production ofstool, the individual need only take a mild laxative, as opposed to acathartic. Non-limiting mild laxatives are described in appl. Ser. No.PCT/US01/32039, at page 37, for example. Thus, the tagging regimen ofthe present invention is less time consuming and more comfortable to theindividual preparing for a predetermined activity, thereby resulting inimproved patient compliance with the preparation process.

In the present invention, the individual may drink a small amounts oftagging agent when undergoing a low residue diet and the hydrationregimen of the present invention patents. Adequate tagging may beobtained with a barium volume ranging between 50 and 750 ml. Thisreduction in barium volume results in all increased patient compliance.A second improvement of patient compliance is related to the fact thatthere was no difference in tagging effectiveness when patients weretaking barium over 1 or 2 days. Reducing the tagging agent intake to Iday will also increase patient compliance.

While the level of compliance of any of these procedures depends in parton the motivation and drive of the individual, compliance neverthelessmay also be influenced by identifiable and controllable factors such asthe ease with which the diet or technique may be utilized, as well asthe taste, appearance, and in general, the desirability of the items tobe eaten.

G. The System and Kit of the Present Invention

The system and/or kit of the present invention represents an improvementover traditional techniques or products used to prepare individuals formedical diagnostic procedures. The present invention is designed tofacilitate user compliance by providing a variety of solid, semi-solidand liquid food items for consumption, together with a tagging agent formarking the colonic residue. Additionally, the present invention isdesigned to improve the user's quality of life by supplying the userwith sufficient caloric intake and nutrition such that daily activitiesmay be undertaken. Also, the residue is sufficiently tagged such that itcan be distinguished from surrounding tissues during a diagnosticprocedure, for example.

In one alternative embodiment, the nutritional dietary system and kit ofthe present invention comprises one or more food items arranged in oneor more separate feedings, for example, three feedings. Examples ofsuitable embodiments, systems and kits of the present invention, aredescribed in International Appl. No. PCT/US01/32039 and U.S. applicationSer. No. 10/177,276, which are incorporated herein by reference.

In one embodiment of the present invention, an individual obtains thepresent invention comprising one or more individually prepackaged fooditems and tagging agents. The invention also comprises instructions forcoordinating the food items for use together as a single dietary system,as well as instructions for coordinating the tagging agent with thedietary system. The instructions may be positioned on one or moresurfaces of the container holding the food items and/or tagging agent,or the instructions may be provided on a separate sheet, or anycombination thereof. Such instructions may specify the frequency thefood items and tagging agent are to be consumed by an individual overtime.

The instructions may also include, for example, instructions forcoordinating the dietary regimen for use together with one or more dosesof a tagging agent. For instance, certain tagging regimens involvedrinking specific volumes of tagging agent over a 24-hour period. Thus,the instructions may specify, for example, the volume of tagging agentto be consumed over time in conjunction with the nutritional dietaryregimen. For example, the instructions may provide that one dose oftagging agent be consumed in the morning, and one dose in the afternoon,and one dose in the evening prior to a predetermined medical activity,such as a medical diagnostic procedure.

The present invention may also provide a container structured to allowfor placement of the food items and the coordinating instructions. Thisenables each of the food items to be placed in the kit, thus making thepresent system easy to follow, which facilitates user compliance. Anon-limiting example of such a container is shown in FIG. 1. In FIG. 1,container (1) contains multiple food items of the present invention.Specifically, nutritional drink (2) is positioned in section (3) locatedat the front of container (1). A first snack food (4) is positioned inadjacent section (5). Another nutritional drink (6), along with abeverage (7) and soup product (8) is positioned in section (9). A secondsnack food (15) is positioned in subsequent section (10). In oneembodiment of the present invention, the snack food (4) or (15) maycomprise a starch food, protein supplement, fruit food or vegetablefood. Another nutritional drink (11), beverage (12) and grain food (13)is positioned in the farthest section (14) relative to the front of thecontainer.

Indicia may be included in at least one of the surfaces of the containerand/or one or more food items. The indicia may take the form of awriting or illustration or both, to assist the individual to readilydistinguish the food items from each other. This feature is especiallyuseful for individuals that are ill, weak or suffer from poor vision, orthat experience difficulty in reading labels found on ordinary foodcontainers. In one embodiment of the present invention, the indicia maycomprise large lettering or illustrations readily in identifiablecolors.

FIG. 5 shows an alternative embodiment wherein the dietary regimen ofthe present invention is used in conjunction with a tagging regimen. Afirst feeding (70) is consumed in the morning, for example, at about8:00 a.m. The first feeding may comprise one nutritional drink. It mayalso comprise 3 to 5 oz of boiled white rice and 200 ml to 250 ml, suchas a water or a fruit drink. A first dose of tagging agent (73) may beconsumed thereafter. A second feeding (72) may be consumed at or aboutmid-day, for example at 12:00 p.m. Second feeding (72) may comprise onesoup product, one nutritional drink and one beverage. After the secondfeeding, the individual may consume a second dose of tagging agent (74).A third feeding (78) may be consumed at about late afternoon or earlyevening, at about 5:00 p.m., for example. Third feeding (78) maycomprise one soup product, one nutritional drink and one beverage. Afterthe third feeding, the individual may consume a third dose of taggingagent. First and second snacks (77, 78) may be consumed between thefirst and second feeding (70, 74), and second and third feedings (72,75), respectively. Each snack may comprise one or more proteinsupplements or starch foods. Such snacks may also comprise a soupproduct, grain food, and fruit or vegetable food.

In reference to FIG. 2, a representative kit of the present invention isshown comprising three feedings. A first feeding (16) is placed in oneportion of the present invention (17), a second feeding (18) is placedin an adjoining section of kit (17) and a third feeding (19) is placedin adjoining section (17). Also, two food items, first snack (20) andsecond snack (21) are placed in an adjacent divided area (17). In thisembodiment, the present invention comprises approximately 2000 calories.Three doses of tagging agent (28-30) may also be placed in kit (17).However, it is understood that the kit may contain one or more doses oftagging agents, or none. Instead, tagging agent may be producedseparately.

In FIG. 2, each feeding represents consumption of one or more fooditems. For example, the first feeding may comprise one nutritional drink(22). The second feeding may comprise one soup product (23), onenutritional drink (24) and one beverage (25). The third feeding maycomprise one soup product (26), one nutritional drink (27) and onebeverage (28). The first and second snacks (20, 21) may comprise oneprotein supplement (29) and one starch food (30), respectively. Theseitems may be consumed between the first and second feedings, and secondand third feedings, respectively.

In reference to FIG. 3, the method/system or kit of the presentinvention may contain one or more food items arranged into three meals.The first feeding (31) is consumed, for example, at about 8:00 a.m. andmay comprise one nutritional drink. A first dosage of tagging agent (36)may be consumed thereafter. A first snack (32) may be provided, andfirst snack (32) may comprise one protein supplement and/or one starchfood. The second feeding (33) may be consumed at about 12:00 p.m. andmay comprise one soup product, one nutritional drink, one fruit food andone beverage. A second dosage of tagging agent (37) may be consumedafter. The third meal (34) may be consumed at about 6:00 p.m. and maycomprise one soup product, one nutritional drink and one beverage. Athird dosage of tagging agent (38) may be consumed thereafter. A secondsnack (35) may be provided, and snack (35) may comprise one proteinsupplement and/or one starch food. First and second snacks (32, 35) maybe consumed between the first and second feeding (31, 33), and secondand third feedings (33, 34), respectively.

Also, the first, second and third feedings (31, 33, 34) may represent abreakfast, lunch and dinner meal, respectively. For example, inreference to FIG. 5, breakfast meal (36) may be placed in one portion ofa kit (37), a lunch meal (38) may be placed in an adjoining section ofkit (37), a dinner meal (39) may be placed in adjoining section of kit(37) and lastly the two snack items, i.e., first snack (40) and secondsnack (41), may be placed in an adjacent divided area of kit (31). Inthis embodiment, the whole kit comprises approximately 2,000 caloriesand may be consumed over about a 24-hour period.

In another embodiment, the present invention is a method for use inpreparing an individual for a predetermined activity. Such isaccomplished by providing the individual one or more food items andtagging agents for consumption prior to a predetermined activity. Thepresent invention may also be carried out by instructing the individualto obtain items, individually or collectively, and consume them. Forexample, a physician may instruct an individual to prepare, purchase orotherwise obtain the one or more food items and doses of tagging agents,individually or collectively, and instruct the individual to consumethese items prior to a predetermined activity and/or pursuant to aregimen.

In another embodiment, the method of the present invention comprises thestep of providing an individual one or more doses of tagging agent andone or more food items arranged in three separate feedings. The methodmay also comprise the step of instructing the individual to prepare,purchase or otherwise obtain the necessary food items, individually orcollectively, to compose these feedings, and consume them pursuant to apredetermined dietary regime and/or prior to a predetermined activity.

In another embodiment, the method of the present invention comprises thestep of providing an individual one or more doses of tagging agent andone or more food items arranged into three specific types of feedings,particularly a breakfast feeding, a lunch feeding and a dinner feeding.

In reference to FIG. 4, a non-limiting embodiment of the method of thepresent invention is disclosed. First, step (64) involves having anindividual undergo the diet of the present invention approximatelytwenty-four hours, or one day, before a predetermined activity,including but not limited to, a diagnostic procedure such ascolonoscopy. Step (64 a) involves the individual undergoing a regimenfor tagging at least some colonic residue in removing food residue fromthe digestive tract. Step (65) involves having the colonoscopy performedapproximately 24 to 36 hours after step (64). In step (65), thecolonoscopy is successful because the stool was sufficiently tagged,such that it could be differentiated from surrounding tissues.

Further, in reference to FIG. 4, in step (64) the individual does notexperience the detrimental effects that are commonly associated with theclear liquid diet known in the prior art, e.g., symptoms oflightheadedness and dizziness due to insufficient calories andnutrition.

first and second feeding (31, 33), and second and third feedings (33,34), respectively.

FIGS. 6 to 12 illustrate a single slice CT scan (Philips AV/FU) of anindividual's colon. For each figure, the slice thickness is 5 mm, tableincrement is 7 mm, and the reconstruction index is 2 mm. Specifically,FIGS. 6 to 8 are colonography images of an individual receiving 3 dosesof tagging agent over a 24-hour period. The doses were 25 ml, 12.5 ml,and 12.5 ml comprising 40% w/v barium sulfate. The individual underwenta bowel cleansing prior to the colonography procedure. FIGS. 9 through10 are also colonography images. In FIG. 9, the individual wasadministered 3×250 ml doses of 2.1% w/v barium sulfate over a 24-hourperiod. Also, the individuals underwent bowel cleansing prior to thecolonography. In FIGS. 11 to 12, the individuals were administered 3×250ml doses of 2.1% w/v barium sulfate over a 24-hour period. During thattime, the patient underwent a low residue diet, in accordance with thepresent invention. Also, the individuals' fluid intake was limited to1.5 to 2.0 liters. Here, the individuals did not undergo a bowelcleansing prior to the colonography procedure.

Generally, in evaluating radiographic images, the radiologist has tointerrogate the data set produced by such images. The radiologisttypically reviews the images at a workstation. In some instances, theimages will be displayed in a 2D axial format. In using the presentinvention, the radiologist can differentiate between retained stool anda polyp due to the presence of tagging agent in the stool. One of thevalues of the present invention is the contribution of creating asetting where the differentiation between stool and an abnormal finding(e.g., polyp) is readily apparent and does not require extensive timeand effort to examine. Further, the radiologist can screen theradiography image to identify the presence of any abnormalities withoutmanipulating the images (e.g., electronically removing the marked stoolfrom the images). This is because the stool is thoroughly marked, andthe usual features of the marked stool are readily distinguishable fromthose of the soft tissue. Consequently, the radiologist spends less timeto evaluate images of colons prepared by the present invention, allowinghim/her to spend more time on other issues that require their expertisein imaging interrogation. The reduction of time to review the imagesalso equates to less “eye strain” by the radiologist improving theiroverall performance and productivity.

Also, the development of Computer Assisted Differentiation (CAD) systemswill be able to utilize the tagging regime of the present invention. Forexample, the images of the colons prepared by the present invention canstrengthen the CAD algorithms to differentiate between retained residueand colonic anomalies. For instance, the tagged stool can beincorporated in the algorithm or subtracted out of the image for CADreview.

VII. EXAMPLES

The invention may be further understood by a consideration of thefollowing examples, which are intended to be purely exemplary of the useof the invention.

Example 1

The following study evaluated the use of barium as the sole taggingagent in the context of prep less CTC. In a Patient Study I, the rangeof highest densities in the fecal residue using barium as the soletagging agent in combination with reduced cathartic cleansing wasevaluated. In Patient Study II of the study the assumptions derived fromthese findings were evaluated in a phantom study. Finally, based uponthese observations, we developed a method of labeling stool with bariumas the sole tagging agent in the unprepped colon. In the perspective ofelectronic cleansing, it was the objective to obtain a sufficiently highdensity of the tagged stool and a sufficiently dry colon.

Patient Study I

A comprehensive test of the invention was performed on 100 patients whohad undergone CTC after a dedicated preparation. Two days before theprocedure, the patients were asked to observe a classic low residuediet. The day before the examination, patients had three mealsbreakfast, lunch and dinner) with a dedicated low residue diet (NutraPrep, E-ZEM, Westbury, N.Y., USA) in order to perform nutritional bowelcleansing. At each meal 250 ml of a 2.1% barium solution (Tagitol,E-Z-EM) was administered. The maximal fluid intake was 3 to 3.5 litersfor that day. The patients were however not obliged to follow theproposed hydration regimen. After dinner, cathartic cleansing of thecolon was performed using magnesium citrate and four Bisacodyl tablets.On the morning of the examination, patients were asked to insert aBisacodyl suppository. No breakfast was allowed on the day of theexamination. CTC was performed in the morning. After relaxation withscopolaminebuthylbromide (Buscopan, Boehringer Ingelheim, Paris, France)and inflation of the colon with room air, single slice helical CT of thecolon was performed with a slice thickness of 5 mm, a 7 mm table feedand a 3 mm reconstruction index. Patients were scanned in supine andprone position. Two radiologists (P.L. and S.G.) reviewed all CTC. Age,gender, examination date and colon length were recorded. The colonlength was measured using central path tracking. In case of collapse orspasm of a colonic segment the path was continued through the collapsedzone. Each colon was reviewed in order to assess the amount of residualstool and fluid and the efficacy of tagging. The residual stool wasmeasured and divided in 3 categories according to size, the largest sizehaving priority over the smaller sizes (1=<5 mm; 2=6 9 mm; 3=>10 mm). Inaccordance with the protocol set forth in Macari et al., Radiology 2001;218: 274-277, the amount of fluid was measured according to itsproportion to the maximum anteroposterior diameter of that segment ofthe colon in which it was detected (1=0% of the lumen; 2=<25%; 3=25−50%;4=>50% of the lumen). On each occasion density measurements (H.U.) ofthe residual stool and fluid were performed. Since the purpose of thestudy was to evaluate the range of highest densities obtained withbarium as the sole tagging agent, ROI density measurements of thevisually best tagged residue were obtained. This was done on a segmentalbasis.

Phantom Study

A plastic bottle with a diameter of 5.5 cm and filled with a 2.1% waterybarium suspension was submerged into a plastic box filled with water,.This phantom was scanned along its longitudinal axis each 24 hours,using the scanning parameters detailed above. In this way circularsections of the bottle with the barium suspension were obtained. On eachoccasion, densities were measured on the axial slices using a circlecovering the entire surface of the section of the bottle except for aperipheral 1 mm ring to avoid partial volume averaging. At each time ahistogram was obtained indicating mean, maximum and minimum densityvalues and the standard deviation (H.U.). These measurements werecompared. The measurements were suspended when there were no significantchanges in densities after 2 consecutive measurements.

Patient Study II

A comprehensive test of the invention was also performed on 3 groups of3 patients, who underwent CTC after a dedicated preparation. Allpatients were asked to observe the dedicated low residue diet the daybefore CTC as described above. In all groups a strict hydration regimenwas followed. In group 1, the beverage consisted of 250 ml of a 2.1%barium suspension at breakfast, lunich and dinner. An additional750-1250 ml of water could be ingested. No fluid intake was permittedafter 8 o'clock p.m. In group 2, patients took in 250 ml of a 4 bariumsuspension at breakfast and 250 ml of a 2.1% barium suspension at lunchand dinner. The same amount of additional beverage was allowed as ingroup 1. In group 3 nutritional cleansing started with 3 aliquots of 50ml of a 4% barium suspension at breakfast, lunch and dinner 2 daysbefore CTC. The day before CTC, the same regimen as in group 1 wasfollowed. There was no cathartic bowel cleansing in any of the patientgroups. In all groups CTC was performed using the same method as inpatient study I. The residual tool and fluid were evaluated as in studyI. In all patients, density measurements were performed of all residue.

Results

Patient Study I

There were 43 female and 57 male patients with ages varying from 36 to90 and with a mean age of 63. Colon length varied from 126 to 231 cmwith a mean length of 164 cm. In total 600 colonic segments wereexamined.

1. Fecal Residue.

No significant relationship between demographic data, colon length,examination date, colon cleanliness, and density of fecal residue orfluid was detected.

-   -   a. Quantity and Size.

In 14 patients, no fecal residue was detected. Fecal residue wasdetected in 217 segments (36.2%) of 86 patients. These fecal residueswere mostly right-sided: Cecum: 66 segments; ascending colon: 59segments. Residue >10 mm were observed in 24 segments (4%). Fecalresidue 6-9 mm was detected in 60 segments (10%). In 133 segments (22%)only residue <5 mm was detected.

-   -   b. Efficacy of Tagging.

In 7 patients (9 segments) non-tagged fecal residue was found, with 5segments having stool 6-9 mm and 2 segments with stool >1 cm.

Density measurements of the tagged stool revealed a very wide range ofdensities from 20 H.U. up to 2890 H.U. The mean highest densities (H.U.)and standard deviations are listed in the table below. Stool Size >1 cm6-9 mm >5 mm Highest mean density 863 SD 800 540 SD 533 268 SD 224

In 59 segments (9.8%), representing 33 patients, at least one fecalresidue with a density of >500 H.U. was detected. These residues weremostly right-sided: Cecum: 16; ascending colon: 17; transverse colon:16.

2. Residual Fluid.

Residual fluid was detected in 82 patients representing 272 colonicsegments (45.3%)(Cecum: 66; ascending colon: 64; transverse colon: 52;descending colon: 50; sigmoid colon: 28; rectum: 12). In 50 of thesesegments over 25% of the colonic lumen was covered on at least 1 axialslice. The residual fluid never reached a density >500 H.U. No more than5 patients (5 segments) had a fluid level with a density >400 H.U. Therewere non-tagged fluid levels in 70 colonic segments (34 patients). Onlyin 3 patients this non-tagged fluid level covered more than 25% of thecolonic lumen on at least one axial slice.

Phantom Study

The changes in the phantom were observed during an 8 week time span. Atthe start the barium suspension in the bottle was homogeneous with amean density of 400 H.U. Gradually the barium barium setteled towardsthe bottom of the bottle ending as a dense layer with a maximum densityof 2895 H.U. In the top of the bottle the barium suspension became lessdense and ended up as a watery solution with a minimum density of 6 H.Uin the top. There was no change of the mean density of the solution.

Patient Study II

In all patients the ceco-ascending colon presented with fecal residue.The descending colon, the sigmoid and the rectum were empty in 4, 5 and3 patients respectively. In all segments there was at least 1residue >10 mm. The largest amount of fecal residue was located in thececo-ascending colon.

Efficacy of Tagging

The mean highest densities of the tagged stool (H.U.) and standarddeviations are listed in the table below. >1 cm 6-9 mm >5 mm Group 11161 SD 208  937 SD 135  616 SD 120 Group 2 1390 SD 111 1450 SD 126  872SD 96 Group 3 1852 SD 353 1483 SD 98 1125 SD 65

In 2 patients (group 2 and 3) there were some very small (<5 mm)non-tagged residues in the right hemi colon. Two patients presented withnon-tagged residue of 1 cm in the rectum. This stool contained air andwas surrounded by a barium ring.

Residual Fluid.

In 3 patients there was a very small fluid level (less than 10% of thecolonic lumen). In all cases this fluid was located in the Cecum. Itconcerned 2 patients from group 2 and 1 from group 3. These fluid levelhad a density of 390, 360 and 420 H.U. respectively.

In patient study I, the efficacy of fecal tagging using barium as thefecal tagging agent in combination with a low residue diet and catharticcleansing based on magnesium citrate was assessed. The present inventionperforms efficacious tagging despite the use of a milder cleansingregimen when compared to the cathartic cleansing used in CTcolonography. The present method resulted in an increased patientcompliance (Lefere P A, Gryspeerdt S S, M D, Dewyspelaere J, BaekelandtM, Van Holsbeeck G B. Dietary fecal tagging as a cleansing method priorto computed tomographic colonography: initial results—polyp detectionand patient acceptance. Radiology 2002; 224: 393-403).

In patient study II the cathartic cleansing was omitted during thepreparation process. Here, a combination of a low residue diet and ahydration control regimen was administered the day before CTcolonography. Tagging based on a 2.1% barium suspension resulted inadequate stool tagging. It is evident that the omission of the catharticcleansing resulted in an increased patient compliance.

Example 2

Fifteen volunteers were scheduled for regular abdominal CT. There were 3male and 6 female patients. The age ranged between 23 and 73 years (meanage: 55.7 years). All patients suffering from vague abdominal pain.According to their preparation, the patients were divided in 2 sections.

1. Section One.

The first section consisted of 9 patients. All patients were preparedwith a dedicated low residue diet presented in a single kit (Nutra Prep,E-Z-EM, Westbury, N.Y., U.S.A.). This diet was designed conceived toperform nutritional bowel cleansing in order to control fat intake andto decrease fecal output. It contained: vanilla flavour shake, fruitjuice, soup, apple sauce, potato poppers and nutrition bars. Thepatients began the diet in the morning of the day before theexamination. At breakfast, the patients consumed the vanilla flavourshake (about 250 ml). Patients could choose one more drink (about 250ml) in the morning. At lunch, the patients ingested another 250 ml ofliquid (vanilla flavour shake, fruit juice or soup). They were alsoallowed to have a supplementary drink (about 250 ml) in the afternoon.At dinner, the patients consumed another 250 ml drink (vanilla flavourshake or soup). The patients were instructed not to consume any moreliquids. This resulted in a fluid intake ranging between 750 ml. and1250 ml. The patients were not required to eat all the contents of thepreparation kit.

Fecal tagging was performed with barium (Tagitol, E-Z-EM, Westbury,N.Y., U.S.A.). Three different regimens of barium intake were followed.Here, the patients were divided in 3 groups of 3 patients (Table 1).Group 1 took in 250 ml of a 2.1% barium suspension at breakfast, lunchand dinner. Group 2 ingested 250 ml of a 4% barium suspension atbreakfast, followed by 1 dose of 250 ml of the 2.1% suspension at lunchand dinner. Group 3 ingested barium over 2 days. Here, two days beforethe exam, the patients ingested 3 doses of 50 ml of the 4% bariumsuspension. On that day, they were allowed to consume their usual meals.The day before the examination, they followed the same tagging regimenas in group 1. This combination of fluid and barium intake resulted in atotal fluid intake ranging between 1.5 and 2 liters the day before theexamination. Patients were not allowed to drink more nor to have anydrinks after 9 p.m. that day. There was no cathartic cleansing in any ofthe patient groups. The morning of the examination the patients couldnot consume anything by mouth.

2. Section Two.

This section consisted of two groups of three patients. All patientswere prepared with a dedicated low residue diet presented in a singlekit (Nutra Prep, E-Z-EM, Westbury, N.Y., U.S.A.). This diet wasconceived to perform nutritional bowel cleansing in order to control fatintake and to decrease fecal output. It contained: vanilla flavourshake, fruit juice, soup, apple sauce, potato poppers and nutritionbars. The diet was started in the morning of the day before theexamination. At breakfast, the patients consumed the vanilla flavourshakeshake (about 250 ml). They could also have a cup of decafeinatedcoffee (about 200 ml). Patients could choose to have 2 more drinks(about 500 ml) in the morning. At lunch, they ingested another 250 ml(vanilla flavour shake, fruit juice or soup). They were also allowed tohave 2 supplementary drinks (about 500 ml) in the afternoon. At dinnerthey had another 250 ml drink (vanilla flavour shake or soup). Afterthis they were not allowed to consume any more liquids. This resulted ina fluid intake ranging between 1450 and 1950 ml. The patients were notrequired to eat all the contents of the preparation kit.

Fecal tagging was performed with barium diluted at 40% weight/volume.Two different regimens of barium intake were used. Accordingly, thepatients were divided in two groups of three patients (group 4 and 5).The day before CTC, group 4 took in 25 ml of the barium suspension atbreakfast and 12.5 ml at lunch and dinner respectively. This resulted in50 ml of barium intake for that day. Group S started their intake ofbarium two days before CTC with 12.5 ml at breakfast, lunch and dinnerrespectively. The next day they followed the same barium regimen asgroup 4.

All patients were examined with a 5 mm slice thickness, a 7 mm tablefeed (pitch about 1.4), and a 3 mm reconstruction index. This resultedin an effective slice thickness of 7 mm. Scans were obtained at 100 mAsand 120 kV. The obtained images were sent to a workstation (Easy Vision,Philips, Best, The Netherlands). In each patient the colon was reviewedin order to assess the amount of residue and the efficacy of tagging.The colon was divided in 6 segments: cecum, ascending colon, transversecolon, descending colon, sigmoid colon, rectum.

A. Amount of Residue

To evaluate the amount of residue 3 different entities were considered:(1) the residual stool; (2) the fluid; and (3) the barium layer. Thisresidual stool was evaluated and divided in 3 categories according toits size (0=no residual stool, 1=residual stool ≦5 mm, 2=residual stool6-9 mm, 3=residual stool >10 mm). To evaluate the quantity of theresidual stool, the number of stool balls was evaluated in each segment.(A=empty, B=1-10, C>10). The fluid was defined as a classic horizontalair-fluid level in the dependent part of the colon with a meniscus atits junction with the colonic wall. In observation of Macari et al., theamount of fluid was assessed on a 1 to 4 basis according to itsproportion to the maximum anteroposterior diameter in that segment ofthe colon it was detected (1=0%, 2=<25%, 3=25-50%, 4=>50% At the sametime the number of slices with fluid was recorded for that segment. Thebarium layer was defined as a layer of barium moulded over thehaustrations and semi-circular folds, evenly distributed on thedependent and non-dependent colonic border, without the classicair-fluid level and without meniscus at its junction with the colonicwall. Segmental evaluation of this barium film was performed. Accordingto its thickness, the barium layer was divided in the same categories asthe residual stool (0=no barium film, 1=thickness <5 mm, 2=thickness 6-9mm, 3=thickness ≧1 cm)

B. Efficacy of Tagging

To evaluate the efficacy of tagging two methods were used. First,according to Callstrom et al. (19), all residue (i.e. residual stool,fluid, barium) with a density ≧150 H.U. was electronically labeled(green) on the axial slices. For each axial slice the same subjectivevisual labeling score of 0%, 25%, 50%, 75% and 100% was used with 0%being non-tagged residue and 100% being completely tagged residue. Thisscore was evaluated per segment. Second, density measurements(Hounsfield Units (H.U.)) of the residue (i.e. fecal residue, fluid,barium film) were performed in all patients on a per-size basis. Theeffective slice thickness being 7 mm, only densities of residue ≧7 mmwere measured. This was done to avoid partial volume averaging.

For residue ≧7 mm a region of interest (ROI) was used. According toSwensen et al., this ROI was round or oval according to the shape of theresidue. In order to avoid partial volume averaging a 2 mm peripheralborder was not included in the ROI. At each time the mean density,maximum and minimum values and the standard deviation were recorded themean values of all measurements (i.e. mean density, maximum and minimumdensity, standard deviation) were calculated per patient and persegment. Per patient group the range of the minimum density values(lowest and highest minimum) was recorded. All density measurements wereperformed on bone-window images.

Results

A total of 90 segments were reviewed. The results concerning the sizeand quantity of the residual stool are listed in table 2 and 3respectively.

A. Section One: There were 13 segments (24.07%), representing 6patients, without residual stool. Patient 5 presented without fecalresidue. In 6 patients, there were 8 segments (14.8%) with only residualstool ≦5 mm. In 29 segments (53.7%) of 8 patients the colon presentedwith more than 10 pieces of stool. There were 22 segments (40.7%)presenting with over 10 pieces of residual stool and with residual stool≧1 cm. Of these segments, 10 (18.5%) were located in the ceco-ascendingcolon and 4 (7.4%) in the rectum.

B. Section Two: There were 12 segments (33%), representing 5 patients,without residual stool. There were 3 segments (8.3%) with only stool ≦5mm. In 18 segments (50%), representing 5 patients, there were more than10 pieces of stool. There were 25 segments (69.4%) presenting with over10 pieces of residual stool and with residual stool ≧1 cm.

The results concerning the fluid levels are listed in table 4. RegardingSection One, 3 patients had a fluid level covering less than 25% of thecolonic lumen. At each time this fluid level was located in the cecum (3segments about 5.5%). It concerned 2 patients from group 2 and 1 patientfrom group 3. In Section Two, there was a fluid level in 5 segments. In4 segments the fluid covered less than 25% of the colonic lumen. In theother segment, this fluid was located in the rectum and covered morethan 50% of the lumen.

The results concerning the barium film are listed in table 5. In SectionOne, 7 patients provided a total of 18 segments (33.3%) with a bariumfilm. In 8 (14.8%) segments the barium layer had a thickness of only ≦5mm. Patient 5, who presented without fecal residue, had a barium film inall but one segment. Taking into account the fecal residue, the fluidand the barium film, 5 segments (9.25%) were completely empty and 2segments (3.7%) presented with only a barium layer <5 mm. In 7 segments(13%) there was only residue <5 mm. This means that in total 14 segments(25.9%) were quite clean (Table 6). In Section Two, 5 patients provideda total of 10 segments with a barium film. This barium film covered lessthan 5 mm in 3 segments. Taking into account the fecal residue, thefluid and the barium film, 5 segments (%) were completely empty. In 3segments (8.3%) there was only residue ≦5 mm. This means that in total14 segments (38.8%) were quite clean (Table 6).

B. Efficacy of Tagging

In total 486 ROI density measurements were performed. The results of thevisual labeling score of the stool are listed in table 7. These scoresvaried between 90 and 100% for all groups, except for the descendingcolon in group 2, where a score of only 71% was obtained. In this groupone patient (patient 4) presented only with stool ≦5 mm in thedescending colon. This stool was not electronically labeled although theresidue appeared as tagged on a visual basis. In this patient the scorefor the descending colon was only 20%. Two patients presented with a 1cm non-tagged residue in the rectum. This non-tagged stool was easilyrecognizable as it contained air and was completely surrounded by abarium ring. The results of the ROI density measurements for residue ≧7mm are listed in table 8. High densities were obtained in all segmentsof all patients. The fluid levels had densities of between 360 and 420H.U. TABLE 1 This table illustrates the different regimen of bariumintake. 2 Days before CTC 1 Day before CTC Breakfast Lunch DinnerBreakfast Lunch Dinner Group 1 250 cc 250 cc 250 cc 2.1% 2.1% 2.1% Group2 250 cc 250 cc 250 cc   4% 2.1% 2.1% Group 3   50 cc   50 cc   50 cc250 cc 250 cc 250 cc  4%  4%  4% 2.1% 2.1% 2.1% Group 4  25 cc 12.5 cc 12.5 cc   40%  40%  40% Group 5 12.5 cc 12.5 cc 12.5 cc  25 cc 12.5 cc 12.5 cc  40% 40% 40%  40%  40%  40%

TABLE 2 Residual Stool: segmental distribution on a per-size basis. As-cending Transverse Descending Sigmoid Patients Cecum Colon Colon ColonColon Rectum 1 3 2-3 1-2-3 3 1 0 2 1-2-3 1-2-3 1 0 1 1-3 3 0 2-3 1-2 3 30 4 1-2 1-3 1-3 1 1-3 1 5 0 0 0 0 0 0 6 0 1 1-2 1-2 0 3 7 3 3 1 2-3 0 38 1-3 1-2-3 1 2-3 1-3 2-3 9 1-2-3 2-3 3 1-3 1-2-3 3 10 1, 2, 3 1, 2 0 01 1, 2 11 1, 2 1, 2, 3 1, 2, 3 1 1, 2, 3 3 12 1, 3 3 1, 2, 3 3 0 2, 3 131, 2 1, 2 1, 2 1, 2 0 3 14 3 0 0 0 0 1 15 1, 2, 3 1, 2 1 0 1, 2 30 = no residual stool;1 = stool ≦5 mm;2 = stool 6-9 mm;3 = stool ≧1 cm.Patients 1-3: group 1;patients 4-6: group 2;patients 7-9: group 3

TABLE 3 Residual Stool: segmental distribution based on the quantity As-cending Transverse Descending Sigmoid Patients Cecum Colon Colon ColonColon Rectum 1 C C C C B A 2 C C C A B C 3 A C C B C A 4 C C C C B B 5 AA A A A A 6 A B C C A C 7 C B B B A B 8 B C C B C C 9 C C C C C C 10 C CA A A C 11 C C C C C B 12 B B C C C B 13 C C C C C B 14 B A A A A A 15 CC B A C BA = No residual stool;B = 1-10;C > 10.Patients 1-3: group 1;patients 4-6: group 2;patients 7-9: group 3.

TABLE 4 Segmental distribution of the fluid levels. As- cendingTransverse Descending Sigmoid Patients Cecum Colon Colon Colon ColonRectum 1 1 1 1 1 1 1 2 1 1 1 1 1 1 3 1 1 1 1 1 1 4 2 1 1 1 1 1 5 2 1 1 11 1 6 1 1 1 1 1 1 7 1 1 1 1 1 1 8 2 1 1 1 1 1 9 1 1 1 1 1 1 10 1 1 1 1 11 11 2 2 1 1 1 1 12 2 1 1 1 1 1 13 1 1 1 1 1 1 14 2 1 1 1 1 4 15 1 1 1 11 11 = 0%;2 = <25% = less than 25% of the colonic lumen covered with fluid on atleast 1 axial slice;3 = 25-50% of the lumen;4 = >50% of the lumen.Patients 1-3: group 1;patients 4-6: group 2;patients 7-9: group 3.

TABLE 5 Segmental distribution of the barium layer, with appreciation ofthe thickness. As- cending Transverse Descending Sigmoid Patients CecumColon Colon Colon Colon Rectum 1 0 1 0 0 0 0 2 1 0 0 0 0 0 3 1, 2 0 1 1,2 0 0 4 1 1 1 0 0 0 5 1, 2 2 2, 3 2 0 2-3 6 1 0 0 0 1 0 7 1, 2, 3 1, 2 20 0 0 8 0 0 0 0 0 0 9 0 0 0 0 0 0 10 2 0 0 0 0 0 11 0 0 1 1 0 0 12 0 0 00 0 0 13 2 0 0 0 2 0 14 2, 3 2, 3 2, 3 2, 3 0 0 15 1 0 0 0 0 00 = No barium layer;1 = thickness ≦5 mm;2 = thickness 6-9 mm; thickness ≧1 cm.Patients 1-3: group 1;patients 4-6: group 2;patients 7-9: group 3.

TABLE 6 Segments presenting without residue, with only residual stool ≦5mm, with only a barium film ≦5 mm. As- cending Transverse DescendingSigmoid Patients Cecum Colon Colon Colon Colon Rectum 1 — — — — 2 1 2 —— 2 1 2 — 3 — — — — — 1 4 — — — 2 — 2 5 — — — — 1 — 6 3 2 — — 3 — 7 — —— — 2 — 8 — — 2 — — — 9 — — — — — — 10 — — 1 1 2 — 11 — — — 2, 3 — — 12— — — — — — 13 — — — — — — 14 — — — — 1 — 15 — — 2 1 1 ——: not applicable.1: empty segments.2: segments with residual stool ≦5 mm.3: segmenst with a barium layer ≦5 mm.

TABLE 8 Table showing the densities of the tagged stool Cecum AscendTransv Descend Sigm Rectum 1 895 955 877 890 812 816 2 843 1015 919 591932 545 3 1094 988 854 861 805 943 4 1541 1526 1466 1353 1468 1064 51040 1007 1022 1172 1267 984

The trials described above show that by combining a low residue diet anda hydration control the day before CT colonography, efficacious taggingof fecal residue in the colon was obatined using barium as the solefecal tagging agent administered at a volume of as less as 50 mladministered over 1 day. Such results were obtained with subject toindividuals to a cathartic cleansing before the predetermined activity.Both the reduction of the barium volume and the short time span ofbarium administration (1 day) will increase patient compliance. Togetherwith the omission of the cathartic cleansing, this could dramaticallyimprove the patient attendance to a screening program for colorectalcancer.

While the above embodiments and descriptions are disclosed in detailsthey are not meant to limit the scope of the claimed invention. Indeed,it will be appreciated by those skilled in the art that various changesand modifications to the subject invention can be made without departingfrom the spirit and scope of the invention. For example, one skilled inthe area would recognize that the present invention encompassesvariations of the embodiments discussed herein. Therefore, differentfood products may be substituted for the specific food productsdescribed herein and the layout of the kit may be modified. Also, fooditems may be substituted among and between each other. Also, theinvention may suitably comprise, consist of or consist essentially ofthe elements described herein. Further, the invention described hereinsuitably may be practiced in the absence of any element which is notspecifically disclosed herein.

1. A method of preparing an individual for a predetermined activity,wherein said predetermined activity requires the tagging of at leastsome colonic residue in the individual's digestive tract, said systemcomprising: (a) administering less than 7 doses of a tagging agent overa 20 to 36 hour administration period; wherein each dose of taggingagent comprises greater than 2% w/v tagging agent; and (b) administeringabout 1 to 4 liters of total fluid over the 20 to 36 hour administrationperiod with the patient free from administration of laxatives orcathartics for at least 24 hours.
 2. The method of claim 1, wherein theadministration of tagging agent is less than 5 doses; the volume of eachdose ranging between 25 to 250 ml; and wherein the total fluid intake is1 to 3 liters over the 20 to 36 hour administration period.
 3. Themethod of claim 1, wherein the administration of tagging agent is 4doses; wherein the volume of one dose comprises at least 30% w/v taggingagent; and the volume of the remaining 3 doses range from about 200 mlto 250 ml and comprises greater than 2% w/v tagging agent.
 4. The methodof claim 1, wherein the administration of tagging agent is 3 doses;wherein the volume of each dose is about 20 ml and comprises about 40%w/v tagging agent.
 5. The method of claims 1-4, wherein the taggingagent is Barium Sulfate.
 6. The method of claim 1, wherein the taggingagent is combined with Sorbitol or Mannitol.
 7. A method for use inpreparing an individual for a predetermined activity; wherein saidpredetermined activity requires the tagging of at least some colonicresidue in the individual's digestive tract, said method comprising thesteps of: (a) administering one or more food items collectivelycomprising: i. at least 100 calories; ii. at least 0.5 grams of dietaryfiber; iii. at least 0.5% of the calories are derived from fat; and iv.about at least 1% by weight of solid material. (b) administering one ormore doses of a tagging agent prior to the predetermined activity.wherein the one or more food items is administered over at least a20-hour period.
 8. The method of claim 7, wherein the tagging agent isBarium Sulfate or Iodine one or more food items collectively comprising:i. more than about 600 calories; ii. less than about 15 grams of dietaryfiber, and iii. less than about 25% of the calories are derived fromfat.
 9. The method of claim 7, wherein the one or more food itemscollectively comprising: i. from about 600 to about 2,000 calories; iifrom about 0.5 grams to about 10 grams of dietary fiber; iii. from about0.5% to about 20% of the calories are derived from fat; and iv. fromabout 10% to about 30% by weight of solid material.
 10. The method ofclaim 7, wherein the tagging agent is combined with Sorbitol orMannitol.
 11. The method of claim 7, wherein the one or more foodcomponents are selected from the group consisting of nutritional drinks,beverages, soup products, starch foods, grain foods, proteinsupplements, fruit foods and vegetable foods.
 12. The method of claim 7,wherein the total fluid intake by the individual is about 1 to 2 liters.13. A method for generating radiography images of one or more sectionsof an individual's gastrointestinal tract for screening, comprising (i)administering to the individual a low residue diet over at least a48-hour period; (ii) administering to the individual one or more dosesof a tagging agent over the at least 48-hour period; (iii) with thepatient free from administration of laxatives or cathartics for at least24 hours, imaging the one or more sections of the individual'sgastrointestinal tract after the administration period; (iv) producing aradiography image of the one or more sections of the individual'sgastrointestinal tract; said image showing stool marked with the taggingagent; (v) screening the radiography image to identify the presence ofany abnormality in the gastrointestinal tract without removing and/orsubtracting the marked stool from the images.
 14. The method of claim13, wherein the images are produced in connection with a predeterminedactivity, including sigmoidscopy, fiberoptic colonscopy, CT colonographyor MR colonography of the individual's colon.
 15. The method of claim13, wherein the administration of tagging agent is less than 5 doses;the volume of each dose ranging between 25 to 250 ml; and wherein thetotal fluid intake is 1 to 3 liters over the 20 to 36 houradministration period.
 16. The method of claim 13, wherein theadministration of tagging agent is 4 doses; wherein the volume of onedose comprises at least 30% w/v tagging agent; and the volume of theremaining 3 doses range from about 200 ml to 230 ml and comprisesgreater than 2% w/v tagging agent.
 17. The method of claim 13, whereinthe administration of tagging agent is 3 doses; wherein the volume ofeach dose is about 20 ml and comprises about 40% w/v tagging agent. 18.The method of claims 15-17, wherein the tagging agent is Barium Sulfate.19. A method of preparing an individual for a predetermined activity;wherein said predetermined activity requires the tagging of at leastsome colonic residue in the individual's digestive tract; said methodcomprising the steps of (i) administering one or more food itemscomprising sufficient tagging agent so that consumption of the one ormore food items by the individual causes the stool to become tagged. 20.The method of claim 19, wherein the one or more ford items areadministered over at least a 24-hour period before the predeterminedactivity.
 21. The method of claim 19 wherein each of the one or morefood items comprises at from about 0.01 g to about 150 g of taggingagent.
 22. The method of claim 20, wherein the total amount of taggingagent consumed by the individual during the 24-hour administrationperiod is at least 1 g.
 23. The method of claim 19, wherein theindividual's total fluid intake during the 24-hour administration periodis 1 to 3 liters.
 24. The method of claims 1, 7, and 19, wherein thepredetermined activity is a fiberoptic colonoscopy, virtual colonoscopy,sigmoidoscopy or barium enema.
 25. The method of claim 7, wherein theone or more food items constitute a first feeding, a second feeding, anda third feeding.
 26. The method of claims 1, 7, 13 and 19, furthercomprising the step of providing a mild laxative regimen prior to thepredetermined activity.
 27. The method of claims 1, 7, and 19 whereinthe last dose is administered to the individual more than 8 hours priorto predetermined activity.